Retinoic acid induces the differentiation of many cell types, such as epithelial cells, mesenchyme cells, teratocarcinoma cells, leukaemia cells and immortalized cell lines such as embryonal carcinoma cells and neuroblastoma cells. RA is a morphogen which specifies axial patterning during embryonic development and which affects neurogenesis, and has been used as an effective therapeutic agent for the treatment of acute promyelocytic leukaemia.
The exact mode of action of retinoic acid is currently unknown, although it is known to be mediated by the nuclear retinoic acid receptors (RARs) (Chambon, P., 1996, FASEB J., 10: 940-959), and it is hypothesised that the diverse effects of RA result from the differential regulation of proteins such as transcription factors, enzymes and growth factor receptors.
Cheung, W. M. W. et al. (1997, J. Neurochem., 68: 1882-1888) have used RNA fingerprinting by arbitrarily primed PCR to identify a large number of genes that are differentially regulated during RA-induced neuronal differentiation. The present inventors have succeeded in isolating, purifying and cloning a novel gene which is down-regulated during RA-induced neuronal differentiation and whose resultant protein product possesses morphogenic/mitogenic properties.